The saliva of every blood-sucking arthropod vector for disease that has been examined contains molecules that have either potent pharmacological or immunosuppressive effects. These molecules aid the vectors also inadvertently enhance the infectivity of the pathogens that these vectors transmit (arthropods probe in the skin for a blood meal and deliver pathogens to the skin without their saliva). The saliva of the sand flay (the vector for leishmaniasis) dramatically augments infection with Leishmania in mice and can determine whether Leishmania is able to successfully establish infection in the host. These observations suggest that it may be possible to vaccinate humans against vector-borne disease by vaccinating against the molecules in vector saliva that allow the pathogen to establish infection in the host. In the previous granting period, the sand fly salivary gene was cloned that encodes the protein (Maxadilan or MAX) that augments infection with Leishmania. Immunization with MAX blocks disease-exacerbating effects of MAX in mice. In this proposal the effects of MAX on relevant cell types involved in the response to infection with Leishmania, and the mechanism by which MAX has these effects will be examined. Furthermore, vaccine protocols will be optimized in mice so that they block transmission of leishmaniasis by sand flies. Lyme disease in a serious health problem in the United States. There are at least 3 different immunosuppressive proteins in the saliva of the tick vector for Lyme disease, Ixodes scapularis. The investigator wishes to clone the genes for these proteins and characterize their protein products as was done for the sand fly protein. In addition, he will determine whether these proteins enhance infection with the etiological agent of Lyme disease, Borrelia burgdorferi, and whether these proteins can be used to develop a transmission blocking vaccine for Lyme disease.